QUESTION: In patients with type 2 diabetes and microalbuminuria, what is the effect of a target driven, long term, intensive,
multifactorial intervention compared with conventional treatment on cardiovascular and microvascular disease?

Setting

Patients

Intervention

80 patients were allocated to intensive treatment involving strict treatment goals with stepwise implementation of behaviour
modification (diet plan, exercise, and smoking cessation) and target driven pharmacological therapy for hyperglycaemia, hypertension,
dyslipidaemia, and microalbuminuria. All patients in the intervention group received either an angiotensin converting enzyme
inhibitor or angiotensin II receptor antagonist. Aspirin was given for secondary prevention of cardiovascular disease. 80
patients were allocated to conventional treatment of risk factors from their general practitioner according to Danish Medical
Association guidelines.

Main outcome measures

The primary outcome was a composite endpoint of death from cardiovascular causes, non-fatal myocardial infarction, revascularisation,
non-fatal stroke, amputation resulting from ischaemia, or vascular surgery for peripheral atherosclerotic artery disease.
Secondary outcomes were development of diabetic nephropathy and development or progression of diabetic retinopathy or neuropathy.

Main results

Analysis was by intention to treat. Intensive treatment was associated with a lower risk than conventional treatment for the
primary composite endpoint, development of diabetic nephropathy, development or progression of retinopathy, and progression
of autonomic neuropathy (table). Treatment groups did not differ for progression of peripheral neuropathy (p=0.66) or rates
of having ≥1 minor hypoglycaemia event (p=0.50) or ≥1 major hypoglycaemia event (p=0.12).

Conclusion

In patients with type 2 diabetes and microalbuminuria, a target driven, long term, intensive multifactorial intervention using
behavioural modification and polypharmacological therapy was more effective than conventional treatment for reducing risk
of cardiovascular and microvascular events.

Commentary

Assistant Professor, School of Nursing Atkinson Faculty of Liberal and Professional Studies York University, Toronto,
Ontario, Canada

With the rising incidence of diabetes creating a health and economic burden, research on the prevention of diabetes related
morbidity and mortality is applicable to all practitioners.1 The findings of the United Kingdom Prospective Diabetes Study showed that stringent glycaemic control improved outcomes and
highlighted the need for interventions to modify the risk of complications.2 In the Steno-2 study, a multifactorial approach (medications and behaviour modification of diet, exercise, and smoking) was
used to modify risk factors associated with diabetes. The sustained improvement in the intensive therapy group over 7.8 years
of follow up enhances the value of the study findings.

Improvements in fat and carbohydrate intake and reductions in HbA1c, serum triglyceride and cholesterol concentrations, systolic and diastolic blood pressure, and albumin excretion rate were
found, but interventions to improve body mass index and increase exercise had little effect. Little information was provided
on the behaviourally directed therapies such as the smoking cessation or exercise programme,3 and one is left with the sense that this was a secondary aspect of the management. However, the researchers emphasise that
education, motivation, and individualised plans were part of the overall strategy. Patients in the intensive therapy group
were seen a mean of 4 times per year at a diabetes centre compared with those in the conventional group who were seen by their
general practitioner. However, without a clear understanding of what occurred during these visits, it is difficult to determine
the relative importance of interventions directed toward self management of lifestyle versus pharmacological treatments. It
is possible that additional gains may result from lifestyle interventions of the same intensity as the pharmacological ones
reported in the Steno-2 study. Such investigations are needed.